Efficacy of Memantine, Donepezil, or Their Association in Moderate-Severe Alzheimer’s Disease: A Review of Clinical Trials

Abstract

Background. Acetylcholinesterase (AChE)/cholinesterase (ChE) inhibitors (Is) and memantine are licensed for symptomatic treatment of mild-moderate and moderate-severe forms of Alzheimer's disease (AD), respectively. High doses of the AChE-I donepezil were licensed in the USA for moderate-severe AD, and the association AChE/ChE-Is plus memantine was proposed for AD at this stage. Objectives. This paper has reviewed evidence from clinical trials of the effectiveness of memantine, donepezil, or the two drugs in association in managing moderate-severe AD. Method. Double-blind, placebo-controlled randomized trials (RCTs) using memantine or donepezil alone or in association versus placebo in moderate-severe AD were reviewed. Analysis done in January 2013 considered the years 2007–2012. Results and Conclusion. Only 83 of the 941 papers selected were considered relevant, and only 13 met the criterion of “adequacy and representativeness.” Memantine and donepezil lead to improvements in moderate-to-severe AD and the choice between the compounds should be based on their contraindications more than on disease severity. No evidence was found of advantages of the association of memantine-donepezil. The heterogeneity of conditions explored by RCTs, the relatively short time of observation (24–52 weeks), and the different cognitive assessment tools used did not allow comparing properly different trials.

Long-Term Effects Of Combined Treatment With Memantine And Donepezil On Alzheimer's Disease Patients: 72-Week Study

“…Previous studies have also indicated that when the course of the disease progresses to moderate or severe levels, combination treatments are more effective than single treatment for delaying the degradation of cognitive functions [12,14,[15][16][17][18][19][20][21][22]. Further, we have reported that memantine administered to patients with moderate to severe AD may inhibit the reduction of cerebral blood flow in the prefrontal area, improve global clinical symptoms, cognitive function and BPSD, and lighten the burden of care placed on caretakers [23].…”

Masquerading as Dementia

“…More recently, a combination drug using memantine and donepezil (Namzaric) was approved by the FDA for moderate to severe Alzheimer's. While the drug combination appeared to be well tolerated when given for several months to Alzheimer's patients, no significant benefits were found when the drug combination was compared to either therapy alone [4].…”

Donepezil-Induced Onset of Rheumatoid Arthritis: Case Report and Literature Review

“…By inhibition of AChE/ChE, the enzymes degrading acetylcholine in the synaptic cleft, they enhance the cholinergic transmission and slow down of the acetylcholine (ACh) catabolism which makes acetylcholine more concentrated [4].…”